Previous research by the principal investigator has shown that certain animal cells proliferate in vitro only if provided with SH compounds (when serum is present in the medium) or with methylthio compounds (in the absence of serum). The methylthio compounds can be provided as mixed disulfides of the type R-S-S-CH3. Fetal calf serum has been shown to contain methyl mercaptan which is liberated by reduction and which is identifiable by gas chromatography-mass spectroscopy. These findings are consistent with the theory that these cells require small alkylthio groups for division, that serum is a source of these groups, and that SH compounds act as carriers to transport the groups into the cells in the form of mixed disulfides. Cells can lose the requirement for these compounds during maintenance in vitro, suggesting that the essential groups can be synthesized endogenously and that endogenous synthesis may be limiting in rapidly dividing cells taken from in vivo sources. It is predicted that the essential groups play a role in the process of mitosis. To further explore the above findings and hypotheses, it is proposed to study: 1. the effect of alkylthio groups in cell division, including their effects on gross proliferation, cellular morphology, and proteins of the mitotic apparatus; 2. the metabolism of these groups in cells, including their biosynthesis, intracellular localization, and catabolism; 3. the effect of analogs of CH3-S- both as substitutes and as antagonists.